Determining the Structural Topology of Nephrin-Receptor-Signaling-Complexes

确定去氧肾上腺素受体信号复合物的结构拓扑

• 批准号: 8325835
• 负责人: Chi Won Pak
• 金额: $ 5.22万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325835
• 关键词: Actins; Adaptor Signaling Protein; Address; Biochemical; Cells; Chronic Kidney Failure; Complex; Dimerization; End stage renal failure; Fluorescence Resonance Energy Transfer; Integral Membrane Protein; Kidney Diseases; Kidney Failure; Lead; Measures; Methods; Molecular; N-WASP protein; NCK adaptor protein 1; Nephrotic Syndrome; Protein Secretion; Proteins; Receptor Signaling; Recruitment Activity; Regulation; Renal function; SH3 Domains; Signal Pathway; Signal Transduction; Tail; Testing; Urine; base; density; glomerular function; in vitro activity; nephrin; novel; podocyte; polymerization

DESCRIPTION (provided by applicant): Signaling by nephrin requires the adaptor protein, Nck, and the actin nucleation-promoting factor, N-WASP, to stimulate actin polymerization necessary for efficient glomerular function. Disruptions to this signaling pathway result in nephrotic syndromes, which are characterized by abnormal secretion of protein into urine and ultimately end-stage renal failure. Clustering of the proteins, nephrin and Nck, have been suggested to be important for efficient signaling, though a mechanistic rationale for this is lacking. Studies from our lab have identified a novel regulation of N-WASP activity through dimerization, which increases N-WASP's activity in vitro by >100- fold. We hypothesize that Nck clustering regulates N-WASP dimerization in nephrin signaling, which we propose to study.

说明书(由申请人提供)：newitin发出的信号需要接头蛋白Nck和肌动蛋白成核促进因子N-WASP来刺激有效的肾小球功能所必需的肌动蛋白聚合。这一信号通路的中断会导致肾病综合征，其特征是蛋白异常分泌到尿液中，最终导致终末期肾功能衰竭。蛋白质的聚集性对于有效的信号传递是很重要的，尽管还缺乏机制上的理论基础。我们实验室的研究发现了一种通过二聚化来调节N-WASP活性的新方法，它可以将N-WASP的体外活性提高100倍。我们假设NCK聚簇调节N-WASP二聚体在neparin信号中的作用，这是我们打算研究的。